Pancreatic adenocarcinoma (PaC) is the fourth-leading cause of cancer death in the US, with 37,170 estimated new cases for 2007 and almost as many deaths. This high mortality rate is due to the fact that PaC is generally detected at an advanced stage, and there is no screening test available. Detection of clinical disease at an earlier stage would effectively impact on patient survival enabling more patients to benefit from surgical resection. Our ultimate goal is to develop and commercialize new, sensitive, specific, non-invasive immunodiagnostic assays based on patient serum for PaC early detection. These assays would improve diagnosis, and disease management. In Phase I we have applied proprietary technologies to identify serum biomarkers for the early detection of PaC. Our innovative antibody-based approach involves: i) a collection of polyclonal antibodies raised against known and unknown human proteins;ii) a proprietary protein array referred to as Matrix Protein Array Technology (MPAT) allowing multiplex analysis of a large number of clinical samples using a large number of antibodies;and iii) sera specimens from patients with PaC, benign and inflammatory conditions of the pancreas, and normal controls. We have selected a number of serum biomarkers that discriminate PaC versus non-PaC. The goal of this Phase II proposal is to achieve validation of the biomarkers identified in Phase I, and to generate the reagents necessary for a monoclonal antibody-based immunodiagnostic assay. Specifically, in Phase II/Year 1 we will screen the biomarkers on 150 serum specimens from PaC and non-PaC controls using the MPAT. Statistical data analysis will enable us to select an optimal biomarker panel that shows statistically significant differential expression in cases versus controls. In Phase II/Year 2 biomarkers will be expressed and purified, and specific monoclonal antibodies against the biomarkers will be generated as reagents for the immunoassay. Phase III will focus on product development, i.e. an ELISA-type immunoassay that will be commercialized in partnership with pharma-diagnostic companies. The proposal is designed for the rapid commercialization of an immunodiagnostic assay for PaC detection, with the support of clinical collaborators, a biostatistics data analysis team, consultants and business advisors to ensure rapid and effective translation of the assay to the patients. As proof of concept and feasibility of our technologies, we provide data encompassing the entire process, from biomarker discovery in lung cancer patient serum, to monoclonal antibody and ELISA-based immunoassay development for the early detection of lung cancer. PUBLIC HEALTH RELEVANCE. Pancreatic cancer is the fourth-leading cause of cancer death in the US, and has the shortest life expectancy of all malignancies when discovered. It is generally detected at an advanced stage, when cancer cannot be treated by surgery alone. The development of a simple immunodiagnostic assay based on patient serum to detect pancreatic cancer would have a profound impact on patient survival and reduce mortality from this disease.